Risk factors and incidence of long-COVID syndrome in hospitalized patients: does remdesivir have a protective effect?

BACKGROUND: The definition of 'long-COVID syndrome' (LCS) is still debated and describes the persistence of symptoms after viral clearance in hospitalized or non-hospitalized patients affected by coronavirus disease 2019 (COVID-19). AIM: In this study, we examined the prevalence and the risk factors of LCS in a cohort of patients with previous COVID-19 and followed for at least 6 months of follow-up. DESIGN: We conducted a prospective study including all hospitalized patients affected by COVID-19 at our center of Infectious Diseases (Vercelli, Italy) admitted between 10 March 2020 and 15 January 2021 for at least 6 months after discharge. Two follow-up visits were performed: after 1 and 6 months after hospital discharge. Clinical, laboratory and radiological data were recorded at each visit. RESULTS: A total of 449 patients were included in the analysis. The LCS was diagnosed in 322 subjects at Visit 1 (71.7%) and in 206 at Visit 2 (45.9); according to the post-COVID-19 functional status scale we observed 147 patients with values 2-3 and 175 with values >3 at Visit 1; at Visit 2, 133 subjects had the score between 2-3 and 73 > 3. In multivariate analysis, intensive care unit (ICU) admission (OR = 2.551; 95% CI = 1.998-6.819; P = 0.019), time of hospitalization (OR = 2.255; 95% CI = 1.018-6.992; P = 0.016) and treatment with remdesivir (OR = 0.641; 95% CI = 0.413-0.782; P < 0.001) were independent predictors of LCS. CONCLUSIONS: Treatment with remdesivir leads to a 35.9% reduction in LCS rate in follow-up. Severity of illness, need of ICU admission and length of hospital stay were factor associated with the persistence of PCS at 6 months of follow-up.

Demonstration of opposing thermal sensitivities in hollow-core fibers with open and sealed ends.

The output phase and propagation time of an optical signal propagating through a hollow-core optical fiber (HCF) drift with changes in environmental temperature significantly less than in conventional optical fibers. In all earlier experimental studies, however, the simplifying assumption was made that the thermo-optic effect of air was negligible. In this Letter, we present, to the best of our knowledge, the first experimental demonstration that the air inside a HCF core can make an appreciable contribution to the fiber's thermal sensitivity with the performance depending on whether the fiber is open to the atmosphere or sealed at both ends (e.g., spliced to solid fiber pigtails). We measure both the sensitivity of the accumulated phase as well as the signal propagation time for both open and sealed HCF and show that these are opposite in sign. Most importantly, we show that the thermal sensitivity contribution from the air inside an open HCF has the sign opposite to the effect of fiber elongation (which is otherwise the dominant effect responsible for the overall thermal sensitivity of HCF). We then go on to show that these two effects can be used to balance each other out in order to achieve zero thermal sensitivity for both accumulated phase and propagation time. We demonstrate this property experimentally over a large spectral range.

Hollow-core fibres for temperature-insensitive fibre optics and its demonstration in an Optoelectronic oscillator.

Many scientific and practical applications require the propagation time through cables to be well defined and known, e.g., an error in the evaluation of signal propagation time in the OPERA experiment in 2011 initially erroneously concluded that Neutrinos are faster than light. In fact, there are many other physical infrastructures such as synchrotrons, particle accelerators, telescope arrays and phase arrayed antennae that also rely on precise time synchronization. Time synchronization is also of importance in new practical applications like autonomous manufacturing (e.g., synchronization of assembly line robots) and upcoming 5G networks. Even when the propagation time through a coaxial cable or optical fibre is carefully calibrated, it is affected by changes in the ambient temperature, posing a serious technological challenge. We show how hollow-core optical fibres can address this issue.

3D-printed polymer antiresonant waveguides for short-reach terahertz applications.

In this work, we present a 3D-printed waveguide that provides effective electromagnetic guidance in the THz regime. The waveguide is printed using low-cost polycarbonate and a conventional fused deposition modeling printer. Light guidance in the hollow core is achieved through antiresonance, and it improves the energy effectively transported to the receiver compared to free space propagation. Our demonstration adds to the field of 3D-printed terahertz components, providing a low-cost way of guiding terahertz radiation.

Low-loss Kagome hollow-core fibers operating from the near- to the mid-IR.

We report the fabrication and characterization of Kagome hollow-core antiresonant fibers, which combine low attenuation (as measured at ∼30 cm bend diameter) with a wide operating bandwidth and high modal purity. Record low attenuation values are reported: 12.3 dB/km, 13.9 dB/km, and 9.6 dB/km in three different fibers optimized for operation at 1 µm, 1.55 µm, and 2.5 µm, respectively. These fibers are excellent candidates for ultra-high power delivery at key laser wavelengths including 1.064 µm and 2.94 µm, as well as for applications in gas-based sensing and nonlinear optics.

Optoelectronic oscillator incorporating hollow-core photonic bandgap fiber.

We demonstrate, to the best of our knowledge, the first optoelectronic oscillator that uses hollow-core photonic bandgap fiber (HC-PBGF) as a delay element of a sufficient length to allow for low-noise operation. We show experimentally that HC-PBGF can improve the temperature stability of the oscillator by a factor of more than 15, as compared to standard optical fiber. We also measured the oscillator's phase noise, allowing evaluation of the suitability of HC-PBGF for this application. Additionally, this Letter also provides, to the best of our knowledge, the first characterization of the temperature stability of a long length (>800 m in our Letter) of low-thermal sensitivity (2 ps/km/K) HC-PBGF wound on a spool.

Optical side scattering radiometry for high resolution, wide dynamic range longitudinal assessment of optical fibers.

Current optical reflectometric techniques used to characterize optical fibers have to trade-off longitudinal range with spatial resolution and therefore struggle to provide simultaneously wide dynamic range (>20dB) and high resolution (<10cm). In this work, we develop and present a technique we refer to as Optical Side Scattering Radiometry (OSSR) capable of resolving discrete and distributed scattering properties of fibers along their length with up to 60dB dynamic range and 5cm spatial resolution. Our setup is first validated on a standard single mode telecoms fiber. Then we apply it to a record-length 11km hollow core photonic band-gap fiber (HC-PBGF) the characterization requirements of which lie far beyond the capability of standard optical reflectometric instruments. We next demonstrate use of the technique to investigate and explain the unusually high loss observed in another HC-PBGF and finally demonstrate its flexibility by measuring a HC-PBGF operating at a wavelength of 2µm. In all of these examples, good agreement between the OSSR measurements and other well-established (but more limited) characterization methods, i.e. cutback loss and OTDR, was obtained.

Dense WDM transmission at 2 µm enabled by an arrayed waveguide grating.

We show, for the first time, dense WDM (8×20 Gbit/s) transmission at 2 µm enabled by advanced modulation formats (4-ASK Fast-OFDM) and the development of key components, including a new arrayed waveguide grating (AWGr) at 2 µm. The AWGr shows -12.8±1.78 dB of excess loss with an 18-dB extinction ratio and a thermal tunability of 0.108 nm/°C.

Accurate calibration of S(2) and interferometry based multimode fiber characterization techniques.

We present a novel method to validate the relative amount of power carried by high order modes in a multimode fiber using a Spatial and Spectral (S(2)) imaging technique. The method can be utilized to calibrate the S(2) set-up and uses Fresnel reflections from a thin glass plate to compare theoretical values with experimental results. We have found that, in the most general case, spectral leakage and sampling errors can lead S(2) to underestimate the multipath interference (MPI) of high order modes by several decibels, thus significantly impairing the result of the measurement. On the other hand, by applying suitable corrections as described in this work, we demonstrate that the S(2) produces MPI estimates that are accurate to within 1dB or better.

MicroStructure Element Method (MSEM): viscous flow model for the virtual draw of microstructured optical fibers.

We propose a new method to accurately model the structural evolution of a microstructured fiber (MOF) during its drawing process, given its initial preform structure and draw conditions. The method, applicable to a broad range of MOFs with high air-filling fraction and thin glass membranes, is an extension of the Discrete Element Method; it determines forces on the nodes in the microstructure to progressively update their position along the neck-down region, until the fiber reaches a final frozen state. The model is validated through simulation of 6 Hollow Core Photonic Band Gap Fibers (HC-PBGFs) and is shown to predict accurately the final fiber dimensions and cross-sectional distortions. The model is vastly more capable than other state of the art models and allows fast exploration of wide drawing parameter spaces, eliminating the need for expensive and time-consuming empirical parameter scans.

100 Gbit/s WDM transmission at 2 µm: transmission studies in both low-loss hollow core photonic bandgap fiber and solid core fiber.

We show for the first time 100 Gbit/s total capacity at 2 µm waveband, using 4 × 9.3 Gbit/s 4-ASK Fast-OFDM direct modulation and 4 × 15.7 Gbit/s NRZ-OOK external modulation, spanning a 36.3 nm wide wavelength range. WDM transmission was successfully demonstrated over 1.15 km of low-loss hollow core photonic bandgap fiber (HC-PBGF) and over 1 km of solid core fiber (SCF). We conclude that the OSNR penalty associated with the SCF is minimal, while a ~1-2 dB penalty was observed after the HC-PBGF probably due to mode coupling to higher-order modes.

X-ray tomography for structural analysis of microstructured and multimaterial optical fibers and preforms.

Specialty optical fibers, in particular microstructured and multi-material optical fibers, have complex geometry in terms of structure and/or material composition. Their fabrication, although rapidly developing, is still at a very early stage of development compared with conventional optical fibers. Structural characterization of these fibers during every step of their multi-stage fabrication process is paramount to optimize the fiber-drawing process. The complexity of these fibers restricts the use of conventional refractometry and microscopy techniques to determine their structural and material composition. Here we present, to the best of our knowledge, the first nondestructive structural and material investigation of specialty optical fibers using X-ray computed tomography (CT) methods, not achievable using other techniques. Recent advances in X-ray CT techniques allow the examination of optical fibers and their preforms with sub-micron resolution while preserving the specimen for onward processing and use. In this work, we study some of the most challenging specialty optical fibers and their preforms. We analyze a hollow core photonic band gap fiber and its preforms, and bond quality at the joint between two fusion-spliced hollow core fibers. Additionally, we studied a multi-element optical fiber and a metal incorporated dual suspended-core optical fiber. The application of X-ray CT can be extended to almost all optical fiber types, preforms and devices.

Cladding pumped few-mode EDFA for mode division multiplexed transmission.

We experimentally demonstrate a few-mode erbium doped fiber amplifier (FM-EDFA) supporting 6 spatial modes with a cladding pumped architecture. Average modal gains are measured to be >20dB between 1534nm-1565nm with a differential modal gain of ~3dB among the mode groups and noise figures of 6-7dB. The cladding pumped FM-EDFA offers a cost effective alternative to core-pumped variant as low cost, high power multimode pumps can be used, and offers performance, scalability and simplicity to FM-EDFA design.

Picometer-scale surface roughness measurements inside hollow glass fibres.

A differential profilometry technique is adapted to the problem of measuring the roughness of hollow glass fibres by use of immersion objectives and index-matching liquid. The technique can achieve picometer level sensitivity. Cross validation with AFM measurements is obtained through use of vitreous silica step calibration samples. Measurements on the inner surfaces of fibre-sized glass capillaries drawn from high purity suprasil F300 tubes show a sub-nanometer roughness, and the roughness power spectrum measured in the range [5 · 10(-3) m(-1) 10(-1) m(-1)] is consistent with the description of the glass surface as a superposition of frozen capillary waves. The surface roughness spectrum of two capillary tubes of differing compositions can be quantitatively distinguished.

Identification of PTEN at the ER and MAMs and its regulation of Ca(2+) signaling and apoptosis in a protein phosphatase-dependent manner.

The tumor suppressor activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10) is thought to be largely attributable to its lipid phosphatase activity. PTEN dephosphorylates the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate to directly antagonize the phosphoinositide 3-kinase-Akt pathway and prevent the activating phosphorylation of Akt. PTEN has also other proposed mechanisms of action, including a poorly characterized protein phosphatase activity, protein-protein interactions, as well as emerging functions in different compartment of the cells such as nucleus and mitochondria. We show here that a fraction of PTEN protein localizes to the endoplasmic reticulum (ER) and mitochondria-associated membranes (MAMs), signaling domains involved in calcium ((2+)) transfer from the ER to mitochondria and apoptosis induction. We demonstrate that PTEN silencing impairs ER Ca(2+) release, lowers cytosolic and mitochondrial Ca(2+) transients and decreases cellular sensitivity to Ca(2+)-mediated apoptotic stimulation. Specific targeting of PTEN to the ER is sufficient to enhance ER-to-mitochondria Ca(2+) transfer and sensitivity to apoptosis. PTEN localization at the ER is further increased during Ca(2+)-dependent apoptosis induction. Importantly, PTEN interacts with the inositol 1,4,5-trisphosphate receptors (IP3Rs) and this correlates with the reduction in their phosphorylation and increased Ca(2+) release. We propose that ER-localized PTEN regulates Ca(2+) release from the ER in a protein phosphatase-dependent manner that counteracts Akt-mediated reduction in Ca(2+) release via IP3Rs. These findings provide new insights into the mechanisms and the extent of PTEN tumor-suppressive functions, highlighting new potential strategies for therapeutic intervention.

Three mode Er3+ ring-doped fiber amplifier for mode-division multiplexed transmission.

We successfully fabricate three-mode erbium doped fiber with a confined Er(3+) doped ring structure and experimentally characterize the amplifier performance with a view to mode-division multiplexed (MDM) transmission. The differential modal gain was effectively mitigated by controlling the relative thickness of the ring-doped layer in the active fiber and pump launch conditions. A detailed study of the modal gain properties, amplifier performance in a MDM transmission system and inter-modal cross-gain modulation and associated transient effects is presented.

Demonstration of amplified data transmission at 2 µm in a low-loss wide bandwidth hollow core photonic bandgap fiber.

The first demonstration of a hollow core photonic bandgap fiber (HC-PBGF) suitable for high-rate data transmission in the 2 µm waveband is presented. The fiber has a record low loss for this wavelength region (4.5 dB/km at 1980 nm) and a >150 nm wide surface-mode-free transmission window at the center of the bandgap. Detailed analysis of the optical modes and their propagation along the fiber, carried out using a time-of-flight technique in conjunction with spatially and spectrally resolved (S2) imaging, provides clear evidence that the HC-PBGF can be operated as quasi-single mode even though it supports up to four mode groups. Through the use of a custom built Thulium doped fiber amplifier with gain bandwidth closely matched to the fiber's low loss window, error-free 8 Gbit/s transmission in an optically amplified data channel at 2008 nm over 290 m of 19 cell HC-PBGF is reported.

73.7 Tb/s (96 x 3 x 256-Gb/s) mode-division-multiplexed DP-16QAM transmission with inline MM-EDFA.

Transmission of a 73.7 Tb/s (96 x 3 x 256-Gb/s) DP-16QAM mode-division-multiplexed signal over 119 km of few-mode fiber transmission line incorporating an inline multi mode EDFA and a phase plate based mode (de-)multiplexer is demonstrated. Data-aided 6 x 6 MIMO digital signal processing was used to demodulate the signal. The total demonstrated net capacity, taking into account 20% of FEC-overhead and 7.5% additional overhead (Ethernet and training sequences), is 57.6 Tb/s, corresponding to a spectral efficiency of 12 bits/s/Hz.

First demonstration and detailed characterization of a multimode amplifier for Space Division Multiplexed transmission systems.

We present the first demonstration of a multimode (two mode-group) erbium-doped fiber amplifier for Space Division Multiplexed (SDM) applications and demonstrate various design and performance features of such devices. In particular we experimentally demonstrate that differential modal gains can be controlled and reduced both by fiber design and control of the pump field distribution. Using a suitably designed fiber we demonstrate simultaneous modal gains of ~20 dB for different pair-wise combinations of spatial and polarization modes in an EDFA supporting amplification of 6 distinct modes.

Robustly single mode hollow core photonic bandgap fiber.

We report the fabrication of a novel type of hollow core photonic bandgap fiber (PBGF) with a small core formed by 3 omitted unit cells in a triangular array of holes. The transmission properties of fibers designed for operation at 1500nm wavelength are investigated both experimentally and through extensive modeling. The novel PBGF structure provides robust single mode guidance and is of particular interest for device applications which require low index bandgap guidance and short device lengths.